Estrogen Receptor Beta Agonist Compounds
Estrogen Receptor Beta Agonists for the treatment of breast, colon, and prostate cancers as well as inflammatory diseases.
There is a large emphasis on the need for novel and more effective cancer therapeutics, since there were nearly 600,000 cancer deaths in the United States in 2016 alone. One method for therapy of prostate, breast, and colon cancer that has been gaining traction is the targeting of estrogen receptors, specifically estrogen receptor beta (ER beta), in cancer cells. The human genome encodes two genes for estrogen receptors: ER alpha and ER beta. ER alpha promotes proliferation of the cancerous tissue, while ER beta counterbalances the proproliferative activities of ER alpha and acts as a tumor suppressor. Since estrogen receptors are overexpressed in these types of cancerous tissues and estrogen receptor beta is overexpressed by around 70% in breast cancer tissue, an anticancer therapy would target estrogen signaling with selective ER beta agonist to selectively activate tumor suppressive properties of ER beta. There are ER beta agonists available, but the affinity and selectivity of these agents are not ideal. To increase the potential therapeutic power of estrogen receptor beta agonists, a compound with enhanced binding affinity needs to be developed.
The Ohio State University researchers, led by Dr. Werner Tjarks, in conjunction with Dr. Petr Bartunek's team at The Institute of Molecular Genetics of the ASCR, designed and developed a library of compounds that target and modulate estrogen receptor beta (ER-beta) activity. Dr. Tjarks’ compounds have enhanced binding affinity to the estrogen receptor as a result of the unique spherical geometry and hydrophobicity character of the compounds. These estrogen receptor beta agonists have shown EC50 values and ER-alpha/ER-beta ratios that are far superior to the industry standard ER-beta agonist, diarylpropionitrile (DPN).